The neuromythology of Parkinson's Disease

Calne, Donald B.; Mizuno, Yoshikuni

doi:10.1016/j.parkreldis.2004.03.006

Cited by 62 publications

(17 citation statements)

References 18 publications

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“…Our consideration of the LB as a finding not specific to PD dementia is further supported by the presence of LBs in other neurological diseases including ataxia telangiectasia and neuroaxonal dystrophy, pantothenate kinase-associated neurodegeneration and Down's Syndrome. Some have even suggested that the traditional view of the LB as responsible for major pathology in PD may be erroneous [24]. The initial findings reported in this study and from the LB presence in diseases other than PD support the view that the “LB” may not be specific to the dementia syndrome of PD.…”

Section: Discussionsupporting

confidence: 68%

Parkinson's disease dementia – A diminished role for the Lewy body

Libow

Frisina

Haroutunian

et al. 2009

Parkinsonism & Related Disorders

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The literature currently views Lewy bodies as central in the pathogenesis of Parkinson's disease dementia (PDD) when Alzheimer's disease (AD) or vascular pathology is not present. Because the neuropathology of PDD is not well understood, the pathological features of PDD were characterized in eighteen PD brain specimens using published criteria for AD, Diffuse Lewy Body Disease (DLBD), and Vascular Disease as a framework. Among the PD dementia (n = 16) subjects, 3 (19%) did not have LBs outside of the brain stem, nor AD or vascular pathology. In two additional cases, one did have rare LBs in the neocortex and cingulate gyrus. However, these two cases did not meet the diagnostic criteria for DLBD. Beyond these 5 cases, the remaining PD dementia subjects fitted a classical pathological profile consistent with AD (38%), vascular disease (12.5%), DLBD (6%), or a combination of these pathologies (12.5%). The findings from this study do not support the hypothesis that LBs are the main substrate for dementia in PD. More research with a larger sample size is needed to determine whether the LB may be a secondary phenomenon and/or an “innocent-bystander”. The entire role of the LB in PD dementia is again brought into question.

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Section: Discussionsupporting

confidence: 68%

Parkinson's disease dementia – A diminished role for the Lewy body

Libow

Frisina

Haroutunian

et al. 2009

Parkinsonism & Related Disorders

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“…Toxicity in these diseases has however often been attributed to oligomeric protein aggregates 43 44 45 46 . In that respect, it remains controversial whether the amyloid deposits themselves are toxic 6 16 17 18 47 48 49 50 51 52 53 54 . In some diseases, inclusion body formation seems neuroprotective.…”

Section: Discussionmentioning

confidence: 99%

“…LBLI may be indicative of cellular dysfunction and death 16 17 but have also been described as harmless, inert or neuroprotective protein aggregates 18 . PD symptoms have been shown to directly correlate with the density of neurons in the substantia nigra pars compacta 19 , but no correlation could be established between the number of LBLI and the severity of disease symptoms 16 . Assuming LBLI are indeed inert, one would expect the affected cells to have a normal life span.…”

mentioning

confidence: 99%

Functionally different α-synuclein inclusions yield insight into Parkinson’s disease pathology

Raiss

Braun

Konings

et al. 2016

Sci Rep

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The formation of α-synuclein (α-S) amyloid aggregates, called Lewy bodies (LBs), is a hallmark of Parkinson’s disease (PD). The function of LBs in the disease process is however still unclear; they have been associated with both neuroprotection and toxicity. To obtain insight into this contradiction, we induced the formation of α-S inclusions, using three different induction methods in SH-SY5Y cells and rat-derived primary neuronal cells. Using confocal and STED microscopy we observed induction-dependent differences in α-S inclusion morphology, location and function. The aggregation of α-S in functionally different compartments correlates with the toxicity of the induction method measured in viability assays. The most cytotoxic treatment largely correlates with the formation of proteasome-associated, juxta-nuclear inclusions. With less toxic methods cytosolic deposits that are not associated with the proteasome are more prevalent. The distribution of α-S over at least two different types of inclusions is not limited to cell models, but is also observed in primary neuronal cells and in human mesencephalon. The existence of functionally different LBs, in vivo and in vitro, gives important insights in the impact of Lewy Body formation on neuronal functioning and may thereby provide a platform for discovering therapeutics.

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“…Intraneuronal Lewy bodies and Lewy neurites composed of the protein α-synuclein are the pathological hallmarks of the disease. However, the neuropathological changes are not confined to the substantia nigra [ 11 ]. This is reflected in a staging system for IPD proposed by Braak [ 12 ].…”

Section: Activated Microglia and Neuroinflammation In The Neuropatholmentioning

confidence: 99%

TSPO imaging in parkinsonian disorders

Gerhard

2016

Clin Transl Imaging

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Microglial activation is a key aspect of the neuroinflammatory process in neurodegenerative disorders including idiopathic and atypical parkinsonian disorders. With positron emission tomography (PET) it has become possible to image this phenomenon in vivo and over the last years patterns of microglia activation corresponding with the known distribution of neuropathological changes in these disorders have been demonstrated using this technique. In addition the effects of interventions aimed at suppressing microglia activation as part of interventional trials have successfully been demonstrated. Current research aims at evaluating PET tracers for microglial activation with more favorable properties than the prototypical [11C]-(R)-PK11195, as well as developing tracers targeting additional parameters of the neuroinflammatory process like astroglial function.

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The neuromythology of Parkinson's Disease

Cited by 62 publications

References 18 publications

Parkinson's disease dementia – A diminished role for the Lewy body

Parkinson's disease dementia – A diminished role for the Lewy body

Functionally different α-synuclein inclusions yield insight into Parkinson’s disease pathology

TSPO imaging in parkinsonian disorders

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